ByByDr. Khaled IbrahimDr. Khaled Ibrahim

Around the age of 40-50, on the average, menstrual cycles

become less regular and ovulation fails. After a few months to a few

years, they stop entirely.

This phase of life beginning with menstrual irregularity and

including the first year after cessation of menstrual flow is termed

the perimenopause. Most women will gain weight, especially in

the lower abdomen, buttocks, and thighs.

The period of permanent cessation of sexual cycle and

diminished female sex hormones to almost none is called

menopause.

MenopauseMenopause

The term menopause is derived from Greek Meno (months) Meno (months)

and pause (cessation). pause (cessation). The word means cessation of

menstruation.

CliamactericCliamacteric which is by dictionary definition is period of life

when fertility and sexual activity decline.

N.B.: Pre menopause:It is the phase before menopause covering a period of 5-10 years before the last menstrual cycle.

Menopause is caused primarily by ovarian failure. i.e., the

ovaries lose their ability to respond to the gonadotropins, mainly

because most, if not all, ovarian follicles and eggs have disappeared

by this time through atresia.

The hypothalamus and anterior pituitary are functioning

relatively normally & the gonadotropins are even secreted in

greater amounts. The main reason for this is that the decreased

plasma estrogen does not exert as much negative feedback on

gonadotropin secretion.

MechanismMechanism

The cause of menopause is “burning out” of the ovaries.

Throughout a woman’s reproductive life, about 400 of the

primordial follicles grow into mature follicles and ovulate,

Hundreds of thousands of ova degenerate.

At about age 45 year, only a few primordial follicles remain to be

stimulated by FSH and LH, and, the production of estrogens by the

ovaries decreases as the number of primordial follicles approaches

zero.

When estrogen production falls below a critical value, the

estrogens can no longer inhibit the production of the gonadotropins

FSH and LH.

Instead, the gonadotropins FSH and LH (mainly FSH) are

produced after menopause in large and continuous quantities,

but as the remaining primordial follicles become atretic, the

production of estrogens by the ovaries falls virtually to zero.

Starting from age 36, ovarian follicular apoptosis accelerates,

leading to a steady decline in ovarian estradiol production. This

loss of ovarian function results in a 90% loss of circulating

estradiol; serum estradiol concentrations are often lower than 20

pg/mL.

A small amount of estrogen usually persists in plasma beyond the

menopause, mainly from peripheral conversion of adrenal

androgens to estrogen, but the level is inadequate to maintain

estrogen-dependent tissues.

However, extragonadal estrogen synthesis increases as a function of

age and body weight, and most of the estradiol is formed by

extragonadal conversion of testosterone. The predominant estrogen

in menopausal women is the weak estrogen estrone, produced

through aromatase conversion of androstenedione.

Changes in gonadotropin and ovarian hormone production

associated with aging. Lower levels of inhibin B and estradiol result

in impaired negative feedback regulation of gonadotropin release,

increasing FSH and LH.

Production of androstenedione and testosterone during early

menopause continues, with some conversion to estradiol by

aromatase activity in adipose tissue. Adrenal-derived

androstenedione is converted to estrone, principally in adipose

tissue.

At the onset of menopause,

1)FSH levels are markedly elevated,

2)LH levels are moderately high, and

3)Estradiol and inhibin levels are low or undetectable.

4)Adrenal androstenedione is the major source of estrogen,

5)Serum testosterone levels fall moderately.

The breasts and genital organs gradually atrophy to a large

degree.

Thinning and dryness of the vaginal epithelium can cause sexual

intercourse to be painful.

Marked decreases in bone mass and strength, termed

osteoporosis, may occur because of net bone resorption and can

result in bone fractures (Chapter 16).

Physiological EffectPhysiological Effect

Bone mass reach peak at the end of their 3rd decade of life.

After 40 years bone resorption exceeds bone formation by 0.5%

per year.

This negative balance increase after menopause to a lose of 5%

of bone per year.

This estrogen deficiency leads to

(1) increased osteoclastic activity in the bones,

(2) decreased bone matrix, and

(3) decreased deposition of bone calcium and phosphate.

In some women, this effect is extremely severe, and the

resulting condition is osteoporosis. Because this can greatly

weaken the bones and lead to bone fracture, especially fracture of

the vertebrae.

Risk factors:

a) Gender: more in women (male to female ratio is 1:3)

b) BMI

c) Race

* high in white women

* moderate in Asian women

* lowest in Black women

d) Family History +ve

e) Life style

f) Smoking

*caffeine intake *alcohol

*increase in protein diet *decrease in Calcium and Vit D intake

g) Steriod Medication: – Exogenous medication & Cushing Syndrome.

• Prevention – improve lifestyle - regular exercise - eliminate smoking & alcohol• Medication a. ERT (Estrogen Replacement Therapy) b. Biphosphonate (Fosamax) that inhibit osteoclastic activity &

minimal S/E c. Raloxifene (Evista) is selective oestrogen receptors

moderator [SERMs] that bind with a high affinity to estrogen receptors. It has some oestrogen like effect e.g. ↑ bone density, ↓LDL Cholesterol [cardioprotective] but act as estrogen antagonist on

endometriam and breast. d. Calcitonin inhibit osteoclastic activity + analgesic effect of e. Calcium Supplement & Vit D.

Sex drive frequently stays the same and may even increase.

The hot flashes so typical of menopause are caused by periodic

sudden increases in body temperature, which induces a feeling of

warmth, dilation of the skin arterioles, and marked sweating; how

estrogen deficiency causes this is unknown.

Regarding cardiovascular diseases, Women have much less

coronary artery disease than men until after menopause, when

the incidence becomes similar in both sexes, a pattern that is due

to the protective effects of estrogen: Estrogen exerts beneficial

actions on plasma cholesterol, and also exerts multiple direct

protective actions on vessel walls.

In some women is emotional instability.

These symptoms are of sufficient magnitude in about 15 % of

women to warrant treatment.

If counseling fails, daily administration of estrogen in small

quantities usually reverses the symptoms, and by gradually

decreasing the dose, postmenopausal women can likely avoid

severe symptoms.

Most of the symptoms associated with menopause, as well as the

increases in and death from coronary artery disease and osteoporosis,

can be reduced by the administration of estrogen.

Recent studies also indicate that estrogen use may reduce the risk

of developing Alzheimer’s disease and may also be useful in the

treatment of this disease.

The desirability of administering estrogen to postmenopausal

women is controversial, however, because of the fact that long-term

estrogen administration (more than 5 years) increases the risk of

developing uterine endometrial cancer and, possibly, breast cancer as

well.

The increased risk of endometrial cancer can be virtually

eliminated by administration of a progestins along with estrogen,

but the progestins does not influence the risk of breast cancer. The

progestins only slightly lessens estrogen’s protective effect against

coronary artery disease.

In conclusion, numerous studies have shown that, overall,

hormone replacement therapy definitely decreases mortality in

postmenopausal women, principally through estrogen’s protective

effects against heart disease. That is, in the average

postmenopausal woman the protection against heart disease (and

osteoporosis) far outweighs the negative effect of increased

cancer.

However, this may not be the case for individual women who

have a family history of breast or endometrial cancer, or who have

another known risk factor for these diseases.

The development of substances (for example, tamoxifen) that

exert some pro-estrogenic and some anti-estrogenic effects. These

drugs are collectively termed selective estrogen receptor modulators

(SERMs) because they activate estrogen receptors in certain tissues

but not in others;

Moreover, in these latter tissues SERMs act as estrogen

antagonists. Obviously, the ideal would be to have a SERM that has

the pro-estrogenic effects of protecting against osteoporosis, heart

attacks, and Alzheimer’s disease, but opposes the development of

breast and uterine cancers.

What makes SERMs possible? One important contributor is that

there exist two distinct forms of estrogen receptors, which are

affected differentially by different SERMs.

Changes in the male reproductive system with aging are less

drastic than those in women.

Once testosterone and pituitary gonadotropin secretions are

initiated at puberty, they continue, at least to some extent,

throughout adult life. There is a steady decrease, however, in

testosterone secretion, beginning at about the age of 40, which

apparently reflects slow deterioration of testicular function and, as

in the female, failure of the gonads to respond to the pituitary

gonadotropins.

Along with the decreasing testosterone levels, both sex drive and

capacity diminish, and sperm become much less motile.

Changes in the male reproductive system with aging are less

drastic than those in women.

Once testosterone and pituitary gonadotropin secretions are

initiated at puberty, they continue, at least to some extent,

throughout adult life. There is a steady decrease, however, in

testosterone secretion, beginning at about the age of 40, which

apparently reflects slow deterioration of testicular function and, as

in the female, failure of the gonads to respond to the pituitary

gonadotropins.

Along with the decreasing testosterone levels, both sex drive and

capacity diminish, and sperm become much less motile.

Despite these events, many men continue to be fertile in their

seventies and eighties.

With aging, some men manifest increased emotional problems,

such as depression, and this is sometimes referred to as “male

menopause” (or male climacteric).

It is not clear, however, what role hormone changes play in this

phenomenon.

Despite these events, many men continue to be fertile in their

seventies and eighties.

With aging, some men manifest increased emotional problems,

such as depression, and this is sometimes referred to as “male

menopause” (or male climacteric).

It is not clear, however, what role hormone changes play in this

phenomenon.

Thank you